Unlike the parent compounds 2-naphthylamine and 4-aminobiphenyl which predominantly lead to cancer of the urinary bladder in most experimental animals, the o-methyl substituted derivatives 3-methyl-2-naphthylamine and 3,2'-dimethyl-4-aminobiphenyl yield colon cancer in male rats and breast cancer in female rats. The o-methyl derivatives are thus of great interest and potential interest since these two types of cancer are amongst the most important in man. In this program we will, in the coming year, synthesize 14C-labeled 3,2'-dimethyl-4-aminobiphenyl to be used for the identification of the pathways of activation and detoxication of this carcinogen in vivo. In addition, attempts will be made at the syntheses of the nitroso and N-hydroxy derivatives of both carcinogens as well as of compounds containing these groups, in which the o-methyl group is replaced by a hydroxymethyl or carboxyl group. These compounds will serve as standards for the identification of in vivo metabolites and will also be used to determine relative activity in Ames assays. Compounds exhibiting mutagenic activity will be subjected to bioassays in rodents.